Influence of C-Terminal Modifications of Bradykinin Antagonists on Their Activity

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Title:Influence of C-Terminal Modifications of Bradykinin Antagonists on Their Activity
Creators:
Prahl, Adam
Wierzba, Tomasz
Winklewski, Pawel
Wszedybyl, Magdalena
Cherek, Maciej
Juzwa, Witold
Lammek, Bernard
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 62, 12, pp. 1940-1946
Uncontrolled Keywords:Peptides, Bradykinin, Blood pressure, B<sub>2</sub> antagonists

Abstract

In the present study we have described the synthesis and some pharmacological properties of four new analogues of bradykinin (BK). Two peptides were designed by substitution of positions 7 and 8 of known B<sub>2</sub> antagonists with <i>N-</i>methyl-L-phenylalanine [Phe(Me)]. The next two analogues were obtained by replacement of D-Phe residue in position 7 of known B<sub>2</sub> antagonist with 1-naphthyl-D-alanine or 2-naphthyl-D-alanine. The antagonistic potency of peptides was assessed by their ability to inhibit vasodepressor response to exogenous bradykinin in conscious rats. Although our studies demonstrated disadvantegous influence of Phe(Me)<sup>7,8</sup> modification for B<sub>2</sub> antagonism, we showed that D-amino acid residue in position 7 of BK antagonists may be replaced by suitable L-amino acid residue. As regards (D-Nal)<sup>7</sup> substitution, we found strikingly different antagonistic potencies of analogues which differ only in the presence of D-1-Nal and D-2-Nal. We assume that it is due to different conformations of these peptides, proving the importance of the shape of the <i>C</i>-terminal part of B<sub>2</sub> antagonists for their activity.

Title:Influence of C-Terminal Modifications of Bradykinin Antagonists on Their Activity
Creators:
Prahl, Adam
Wierzba, Tomasz
Winklewski, Pawel
Wszedybyl, Magdalena
Cherek, Maciej
Juzwa, Witold
Lammek, Bernard
Uncontrolled Keywords:Peptides, Bradykinin, Blood pressure, B<sub>2</sub> antagonists
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:62
Number:12
Page Range:pp. 1940-1946
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19971940UNSPECIFIED
ID Code:1267
Item Type:Article
Deposited On:06 Feb 2009 17:08
Last Modified:06 Feb 2009 16:08

Citation

Prahl, Adam; Wierzba, Tomasz; Winklewski, Pawel; Wszedybyl, Magdalena; Cherek, Maciej; Juzwa, Witold; Lammek, Bernard (1997) Influence of C-Terminal Modifications of Bradykinin Antagonists on Their Activity. Collection of Czechoslovak Chemical Communications, 62 (12). pp. 1940-1946. ISSN 0010-0765

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